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Demoralization has been described as a psychological state characterized by helplessness, hopelessness, a sense of failure and the inability to cope.

Methods

We conducted a systematic review with qualitative data analysis following PRISMA criteria with the following aims: to review validated assessment instruments of the demoralization syndrome, report main findings regarding demoralization as measured by validated instruments that emerge in the literature, compare and report evidence for the clinical utility of the identified instruments. Utilizing the key word ‘demoralization’ in PubMed and PsycINFO databases, an electronic search was performed, supplemented by Web of Science and manual searches. Study selection criteria included the assessment of medical patients and use of instruments validated to assess demoralization. Seventy-four studies were selected.

Results

Four instruments emerged in the literature. Main findings concern prevalence rates of demoralization, evidence of discriminant validity from major depression, factors associated with demoralization and evidence of clinical utility. The instruments vary in their definition, the populations they aim to assess, prevalence rates they estimate and their ability to discriminate between different conditions. Nonetheless, demoralization appears to be a distinctive psychological state characterized by helplessness, hopelessness, giving up and subjective incompetence. It is not limited to life-threatening diseases such as cancer, but may occur in any type of clinical situation. It is associated with stress and adverse health outcomes.

Conclusions

Studies addressing the incremental value of demoralization in psychiatry and psychology are needed. However, demoralization appears to entail specific clinical features and may be a distinct condition from major depression.

There is growing interest in glutamatergic agents in depression, particularly ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. We aimed to assess the efficacy of ketamine in major depressive episodes.

Method

We searched EMBASE, PsycINFO, CENTRAL, and Medline from 1962 to January 2014 to identify double-blind, randomized controlled trials with allocation concealment evaluating ketamine in major depressive episodes. Clinical remission, response and depressive symptoms were extracted by two independent raters. The primary outcome measure was clinical remission at 24 h, 3 days and 7 days post-treatment. Analyses employed a random-effects model.

Our meta-analysis suggests that single administrations ketamine are efficacious in the rapid treatment of unipolar and bipolar depression. Additional research is required to determine optimal dosing schedules, route, treatment schedules, and the potential efficacy of other glutamatergic agents.

Taxometric procedures, model-based clustering and latent variable mixture modeling (LVMM) are statistical methods that use the inter-relationships of observed symptoms or questionnaire items to investigate empirically whether the underlying psychiatric or psychological construct is dimensional or categorical. In this review we show why the results of such an investigation depend on the characteristics of the observed symptoms (e.g. symptom prevalence in the sample) and of the sample (e.g. clinical, population sample). Furthermore, the three methods differ with respect to their assumptions and therefore require different types of a priori knowledge about the observed symptoms and their inter-relationships. We argue that the choice of method should optimally match and make use of the existing knowledge about the data that are analyzed.

The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) has found that the proportional elevation in the US Army enlisted soldier suicide rate during deployment (compared with the never-deployed or previously deployed) is significantly higher among women than men, raising the possibility of gender differences in the adverse psychological effects of deployment.

Method

Person-month survival models based on a consolidated administrative database for active duty enlisted Regular Army soldiers in 2004–2009 (n = 975 057) were used to characterize the gender × deployment interaction predicting suicide. Four explanatory hypotheses were explored involving the proportion of females in each soldier's occupation, the proportion of same-gender soldiers in each soldier's unit, whether the soldier reported sexual assault victimization in the previous 12 months, and the soldier's pre-deployment history of treated mental/behavioral disorders.

Results

The suicide rate of currently deployed women (14.0/100 000 person-years) was 3.1–3.5 times the rates of other (i.e. never-deployed/previously deployed) women. The suicide rate of currently deployed men (22.6/100 000 person-years) was 0.9–1.2 times the rates of other men. The adjusted (for time trends, sociodemographics, and Army career variables) female:male odds ratio comparing the suicide rates of currently deployed v. other women v. men was 2.8 (95% confidence interval 1.1–6.8), became 2.4 after excluding soldiers with Direct Combat Arms occupations, and remained elevated (in the range 1.9–2.8) after adjusting for the hypothesized explanatory variables.

Conclusions

These results are valuable in excluding otherwise plausible hypotheses for the elevated suicide rate of deployed women and point to the importance of expanding future research on the psychological challenges of deployment for women.

The selection hypothesis posits that the increased rates of psychosis observed among migrants are due to selective migration of people who are predisposed to develop the disorder. To test this hypothesis, we examined whether risk factors for psychosis are more prevalent among future emigrants.

Method

A cohort of 49 321 Swedish military conscripts was assessed at age 18 years on cannabis use, IQ, psychiatric diagnosis, social adjustment, history of trauma and urbanicity of place of upbringing. Through data linkage we examined whether these exposures predicted emigration out of Sweden. We also calculated the emigrants' hypothetical relative risk compared with non-emigrants for developing a non-affective psychotic disorder.

Multiple pathway models of attention deficit hyperactivity disorder (ADHD) suggest that this disorder is the behavioural expression of dysfunction in one of several separable brain systems. One such model focuses on the brain systems underlying cognitive control, timing and reward sensitivity. It predicts separable subgroups among individuals with ADHD, with performance deficits in only one of these domains. We used latent class analysis (LCA) to identify subgroups of individuals with ADHD based on their overall pattern of neuropsychological performance, rather than grouping them based on cut-off criteria. We hypothesized that we would find separable subgroups with deficits in cognitive control, timing and reward sensitivity respectively.

Method

Ninety-six subjects with ADHD (of any subtype) and 121 typically developing controls performed a battery assessing cognitive control, timing and reward sensitivity. LCA was used to identify subgroups of individuals with ADHD with a distinct neuropsychological profile. A similar analysis was performed for controls.

Results

Three subgroups represented 87% of subjects with ADHD. Two of our three hypothesized subgroups were identified, with poor cognitive control and timing. Two of the ADHD subgroups had similar profiles to control subgroups, whereas one subgroup had no equivalent in controls.

Conclusions

Our findings support multiple pathway models of ADHD, as we were able to define separable subgroups with differing cognitive profiles. Furthermore, we found both quantitative and qualitative differences from controls, suggesting that ADHD may represent both categorical and dimensional differences. These results show that by addressing heterogeneity in ADHD, we can identify more homogeneous subsets of individuals to further investigate.

Structured interviews and questionnaires are important tools to screen for major depressive disorder. Recent research suggests that, in addition to studying the mean level of total scores, researchers should focus on the dynamic relations among depressive symptoms as they unfold over time. Using network analysis, this paper is the first to investigate these patterns of short-term (i.e. session to session) dynamics for a widely used psychological questionnaire for depression – the Beck Depression Inventory (BDI-II).

Method

With the newly developed vector autoregressive (VAR) multilevel method we estimated the network of symptom dynamics that characterizes the BDI-II, based on repeated administrations of the questionnaire to a group of depressed individuals who participated in a treatment study of an average of 14 weekly assessments. Also the centrality of symptoms and the community structure of the network were examined.

Results

The analysis showed that all BDI-II symptoms are directly or indirectly connected through patterns of temporal influence. In addition, these influences are mutually reinforcing, ‘loss of pleasure’ being the most central item in the network. Community analyses indicated that the dynamic structure of the BDI-II involves two clusters, which is consistent with earlier psychometric analyses.

Conclusion

The network approach expands the range of depression research, making it possible to investigate the dynamic architecture of depression and opening up a whole new range of questions and analyses. Regarding clinical practice, network analyses may be used to indicate which symptoms should be targeted, and in this sense may help in setting up treatment strategies.

There is an appreciable overlap in the clinical presentation, epidemiology and treatment response of the two major psychotic disorders – schizophrenia and bipolar disorder. Nevertheless, the shared neurobiological correlates of these two disorders are still elusive. Using diffusion tensor imaging (DTI), we sought to identify brain regions which share altered white-matter connectivity across a clinical spectrum of psychotic disorders.

Method

A sample of 41 healthy controls, 62 patients in a clinically stable state of an established psychotic disorder (40 with schizophrenia, 22 with bipolar disorder) were studied using DTI. Tract-based spatial statistics (TBSS) was used in order to study group differences between patients with psychosis and healthy controls using fractional anisotropy (FA). Probabilistic tractography was used in order to visualize the clusters that showed significant differences between these two groups.

Results

The TBSS analysis revealed five clusters (callosal, posterior thalamic/optic, paralimbic, fronto-occipital) with reduced FA in psychosis. This reduction in FA was associated with an increase in radial diffusivity and a decrease in mode of anisotropy. Factor analysis revealed a single white-matter integrity factor that predicted social and occupational functioning scores in patients irrespective of the diagnostic categorization.

Conclusions

Our results show that a shared white-matter dysconnectivity links the two major psychotic disorders. These microstructural abnormalities predict functional outcome better than symptom-based diagnostic boundaries during a clinically stable phase of illness, highlighting the importance of seeking shared neurobiological factors that underlie the clinical spectrum of psychosis.

Evidence suggests some overlap between the pathological use of food and drugs, yet how impulsivity compares across these different clinical disorders remains unclear. Substance use disorders are commonly characterized by elevated impulsivity, and impulsivity subtypes may show commonalities and differences in various conditions. We hypothesized that obese subjects with binge-eating disorder (BED) and abstinent alcohol-dependent cohorts would have relatively more impulsive profiles compared to obese subjects without BED. We also predicted decision impulsivity impairment in obesity with and without BED.

Method.

Thirty obese subjects with BED, 30 without BED and 30 abstinent alcohol-dependent subjects and age- and gender-matched controls were tested on delay discounting (preference for a smaller immediate reward over a larger delayed reward), reflection impulsivity (rapid decision making prior to evidence accumulation) and motor response inhibition (action cancellation of a prepotent response).

Results.

All three groups had greater delay discounting relative to healthy volunteers. Both obese subjects without BED and alcohol-dependent subjects had impaired motor response inhibition. Only obese subjects without BED had impaired integration of available information to optimize outcomes over later trials with a cost condition.

Conclusions.

Delay discounting appears to be a common core impairment across disorders of food and drug intake. Unexpectedly, obese subjects without BED showed greater impulsivity than obese subjects with BED. We highlight the dissociability and heterogeneity of impulsivity subtypes and add to the understanding of neurocognitive profiles across disorders involving food and drugs. Our results have therapeutic implications suggesting that disorder-specific patterns of impulsivity could be targeted.

MEG was used to measure induced gamma and evoked responses to a visual grating stimulus, known to be a potent inducer of primary visual gamma oscillations, in 15 individuals with remitted SABP, defined using Research Diagnostic Criteria, and 22 age- and sex-matched healthy controls.

Results.

Individuals with SABP demonstrated increased sustained visual cortical power in the gamma band (t35 = −2.56, p = 0.015) compared to controls. There were no group differences in baseline gamma power, transient or sustained gamma frequency, alpha band responses or pattern onset visual-evoked responses.

Conclusions.

Gamma power is increased in remitted SABP, which reflects an abnormality in the cortical inhibitory-excitatory balance. Although an interaction between gamma power and medication can not be ruled out, there were no group differences in evoked responses or baseline measures. Further work is needed in other clinical populations and at-risk relatives. Pharmaco-magnetoencephalography studies will help to elucidate the specific GABA and glutamate pathways affected.

Increasing evidence suggests that autism is associated with abnormal white-matter (WM) anatomy and impaired brain ‘connectivity’. While myelin plays a critical role in synchronized brain communication, its aetiological role in autistic symptoms has only been indirectly addressed by WM volumetric, relaxometry and diffusion tensor imaging studies. A potentially more specific measure of myelin content, termed myelin water fraction (MWF), could provide improved sensitivity to myelin alteration in autism.

Method

We performed a cross-sectional imaging study that compared 14 individuals with autism and 14 age- and IQ-matched controls. T1 relaxation times (T1), T2 relaxation times (T2) and MWF values were compared between autistic subjects, diagnosed using the Autism Diagnostic Interview – Revised (ADI-R), with current symptoms assessed using the Autism Diagnostic Observation Schedule (ADOS) and typical healthy controls. Correlations between T1, T2 and MWF values with clinical measures [ADI-R, ADOS, and the Autism Quotient (AQ)] were also assessed.

Results

Individuals with autism showed widespread WM T1 and MWF differences compared to typical controls. Within autistic individuals, worse current social interaction skill as measured by the ADOS was related to reduced MWF although not T1. No significant differences or correlations with symptoms were observed with respect to T2.

Conclusions

Autistic individuals have significantly lower global MWF and higher T1, suggesting widespread alteration in tissue microstructure and biochemistry. Areas of difference, including thalamic projections, cerebellum and cingulum, have previously been implicated in the disorder; however, this is the first study to specifically indicate myelin alteration in these regions.

Genetic and environmental factors contribute to the risk of depression and several studies have noted an association between tobacco smoke and depression. Cadmium is a neurotoxicant and the main source of non-occupational exposure is tobacco smoke.

Method.

We conducted a cross-sectional analysis of data from 2892 young adult (aged 20–39 years) participants of the National Health and Nutrition Examination Survey (NHANES) 2007–2010. Multivariate logistic regressions, adjusted for age, sex, race/ethnicity, education, poverty income ratio (PIR), obesity, alcohol intake, blood lead (BPb) and smoking status, were used to analyze the association between blood cadmium (BCd) and depressive symptoms, as determined by the score on the nine-item Patient Health Questionnaire (PHQ-9).

Results.

Individuals in the highest BCd quartile had higher odds of having depressive symptoms [odds ratio (OR) 2.79, 95% confidence interval (CI) 1.84–4.25] than those in the lowest BCd quartile. Smoking status, but not BPb, was statistically significantly associated with depressive symptoms. Stratification by smoking status found that BCd was significantly associated with depressive symptoms in both non-smokers (OR 2.91, 95% CI 1.12–7.58) and current smokers (OR 2.69, 95% CI 1.13–6.42).

Conclusions.

This is the first study to report an association between BCd levels and depressive symptoms using a nationally representative sample. The association of cadmium with depressive symptoms was independent of smoking status. If this association is further confirmed, the continued efforts at reducing cadmium exposures, mainly through tobacco smoking cessation programs, may decrease the incidence of depression.

Magnetic resonance imaging (MRI) studies have shown that brain abnormalities in psychosis might be progressive during the first years of illness. We sought to determine whether first-episode psychosis (FEP) subjects show progressive regional grey matter (GM) changes compared with controls, and whether those changes are associated with diagnosis, illness course or antipsychotic (AP) use.

Method.

Thirty-two subjects with first-episode schizophrenia-spectrum disorders (FESZ), 24 patients with first-episode affective psychoses (FEAP) and 34 controls recruited using a population-based design underwent structural MRI scanning at baseline and at a 5-year follow-up. Regional GM volumes were assessed with voxel-based morphometry (VBM). Patients were treated at community settings, and about half of them remained mainly untreated.

Results.

No significant progressive changes in GM regional volumes were observed in either the FESZ or FEAP group overall. However, FESZ subjects with a non-remitting course showed GM decrements in the left superior temporal gyrus (STG) and insula relative to remitted FESZ subjects. Non-remitted FEAP subjects exhibited a GM decrease in the dorsolateral prefrontal cortex (DLPFC) bilaterally in comparison to remitted FEAP subjects. Among FESZ subjects, AP use was associated with regional GM decrements in the right insula and increments in the cerebellum.

Conclusions.

Our results suggest that the progression of brain abnormalities in FEP subjects is restricted to those with a poor outcome and differs between diagnosis subgroups. AP intake is associated with a different pattern of GM reductions over time.

The post-pubertal association of female gender with emotional disorder is a robust finding. However, studies exploring the association of gender and emotional disorders before puberty are few and present diverging results. The aim of this study was to present gender-specific incidence rates of emotional disorders throughout childhood.

Method

This is a population-based cohort study of 907 806 Danish 3- to 18-year-olds. The outcome was assignment of an emotional disorder diagnosis based on in-patient and out-patient data from The Danish Psychiatric Central Register. Outcome measures were incidence rates and cumulative incidences for unipolar depressive disorder (ICD-10: F32–F33), anxiety disorders (ICD-10: F40–F42), and emotional disorders with onset specific to childhood (ICD-10: F93).

Results

Pre-pubertal incidence rates for depressive and anxiety disorders were higher for boys than girls. At age 12 years the pattern reversed. The cumulative incidence for any emotional disorder (F32–F33, F40–F42, F93) on the 11th birthday was 0.52% (95% CI 0.50–0.55) for boys and 0.31% (95% CI 0.29–0.33) for girls. On the 19th birthday cumulative incidence was 2.33% (95% CI 2.24–2.43) for boys and 3.77% (95% CI 3.64–3.90) for girls. The pre-pubertal male preponderance was also significant for depressive disorders (F32–F33, p = 0.00144) and anxiety disorders (F40–F42, F93, p < 0.00001) separately.

Conclusions

Emotional disorders seem to display a male preponderance before the age of 12 years and a female preponderance thereafter. Studies exploring this gender–age interaction are needed. Still, the results question the general assumption that females throughout the lifespan are more at risk for emotional disorders than males.

Brain-derived neurotrophic factor (BDNF) is an important regulator of synaptogenesis and synaptic plasticity underlying learning. However, a relationship between circulating BDNF levels and brain activity during learning has not been demonstrated in humans. Reduced brain BDNF levels are found in schizophrenia and functional neuroimaging studies of probabilistic association learning in schizophrenia have demonstrated reduced activity in a neural network that includes the prefrontal and parietal cortices and the caudate nucleus. We predicted that brain activity would correlate positively with peripheral BDNF levels during probabilistic association learning in healthy adults and that this relationship would be altered in schizophrenia.

We found a positive correlation between circulating plasma BDNF levels and brain activity in the parietal cortex in healthy adults. There was no relationship between plasma BDNF levels and task-related activity in the prefrontal, parietal or caudate regions in schizophrenia. A direct comparison of these relationships between groups revealed a significant diagnostic difference.

Conclusions.

This is the first study to show a relationship between peripheral BDNF levels and cortical activity during learning, suggesting that plasma BDNF levels may reflect learning-related brain activity in healthy humans. The lack of relationship between plasma BDNF and task-related brain activity in patients suggests that circulating blood BDNF may not be indicative of learning-dependent brain activity in schizophrenia.

Peer deviance (PD) is associated with risk for drug abuse (DA). Is this association causal?

Method.

DA was recorded in official records. PD was defined as the percentage of peers residing in small communities with future DA registrations. We examined offspring in families whose community PD changed when the offspring was 0–15 years of age and then examined families where cousins or siblings differed in their years of exposure to low or high PD communities.

Results.

The duration of exposure to PD was strongly associated with future DA. Co-relative analyses for families whose exposure to PD declined suggested that the PD–DA association was largely non-causal. Within full-sibling pairs in such families, the length of exposure to low PD environments was unrelated to risk for DA. By contrast, co-relative analyses in families where exposure to PD increased over time indicated that the PD–DA association was largely causal. In such families, siblings who differed in the duration of their exposure to high PD differed in their risk for subsequent DA. These results were replicated in families whose PD changed because they moved or because of changes in the community in which they resided.

Conclusions.

Within families whose social environment is improving over time, the association between PD exposure and offspring DA outcomes is not causal but is due to familial confounding. Within families whose social environment is deteriorating, the PD–DA association seems to be largely causal. Our measure of PD may also reflect broader aspects of the community environment beyond peers.

The medial forebrain bundle (MFB) is an important pathway of the reward system. Two branches have been described using diffusion magnetic resonance imaging (MRI)-based tractography: the infero-medial MFB (imMFB) and the supero-lateral MFB (slMFB). Previous studies point to white-matter microstructural alterations of the slMFB in major depressive disorder (MDD) during acute episodes. To extend this finding, this study investigates whether white-matter microstructure is also altered in MDD patients that are in remission. Further, we explore associations between diffusion MRI-based metrics of white-matter microstructure of imMFB, slMFB and hedonic tone, the ability to derive pleasure.

Method.

Eighteen remitted depressed (RD) and 22 never depressed (ND) participants underwent high angular resolution diffusion-weighted imaging (HARDI) scans. To reconstruct the two pathways of the MFB (imMFB and slMFB) we used the damped Richardson–Lucy (dRL) algorithm. Mean fractional anisotropy (FA) was sampled along the tracts.

Results.

Mean FA of imMFB, slMFB and a comparison tract (the middle cerebellar peduncle) did not differ between ND and RD participants. Hedonic capacity correlated negatively with mean FA of the left slMFB, explaining 21% of the variance.

Conclusions.

Diffusion MRI-based metrics of white-matter microstructure of the MFB in RD do not differ from ND. Hedonic capacity is associated with altered white-matter microstructure of the slMFB.

Domestic and sexual violence are significant public health problems but little is known about the extent to which men and women with severe mental illness (SMI) are at risk compared with the general population. We aimed to compare the prevalence and impact of violence against SMI patients and the general population.

Method

Three hundred and three randomly recruited psychiatric patients, in contact with community services for ⩾1 year, were interviewed using the British Crime Survey domestic/sexual violence questionnaire. Prevalence and correlates of violence in this sample were compared with those from 22 606 general population controls participating in the contemporaneous 2011/12 national crime survey.

Compared to the general population, patients with SMI are at substantially increased risk of domestic and sexual violence, with a relative excess of family violence and adverse health impact following victimization. Psychiatric services, and public health and criminal justice policies, need to address domestic and sexual violence in this at-risk group.